Clinical Report: Treatment Duration and Cost-Effectiveness of Third-Line Therapies in Advanced Colorectal Cancer

Overview

In a real-world cohort of advanced colorectal cancer patients receiving third-line therapy, immune checkpoint inhibitors (ICI) demonstrated longer treatment persistence compared to regorafenib or trifluridine/tipiracil (Rego/Tri), but at substantially higher costs. Time to treatment discontinuation (TTD) was used as a pragmatic endpoint to assess treatment durability, revealing a trade-off between clinical benefit and economic viability of ICIs in routine practice.

Background

Colorectal cancer remains a leading cause of cancer mortality in the US, with many patients progressing to advanced disease despite standard first- and second-line treatments. Third-line options such as regorafenib and trifluridine/tipiracil offer modest survival benefits, while immune checkpoint inhibitors have emerged as promising therapies particularly for MSI-H or dMMR tumors. However, real-world data on the clinical outcomes and cost-effectiveness of ICIs in broader CRC populations are limited. The NIH All of Us Research Program provides a diverse, large-scale real-world dataset to evaluate these therapies in routine clinical settings.

Data Highlights

Key Findings

• Immune checkpoint inhibitors were associated with longer treatment persistence compared to regorafenib or trifluridine/tipiracil in third-line advanced colorectal cancer.
• ICI therapies incurred substantially higher healthcare costs than Rego/Tri regimens.
• Time to treatment discontinuation served as a practical real-world endpoint reflecting treatment durability amid incomplete survival data.
• Real-world cost-effectiveness analyses highlighted a tension between clinical benefit and affordability of immunotherapy in later-line CRC care.
• Incomplete biomarker documentation in real-world data complicates precision oncology implementation and economic assessments.
• The NIH All of Us Research Program enabled evaluation of diverse, nationally distributed patient populations but also revealed data completeness challenges.

Clinical Implications

Clinicians should weigh the longer treatment durability of ICIs against their substantially higher costs when selecting third-line therapies for advanced colorectal cancer. Real-world data underscore the need for improved biomarker testing and documentation to guide precision oncology and optimize resource utilization. Policymakers and healthcare systems must address economic barriers to enable broader access to effective immunotherapies in routine practice.

Conclusion

This study provides real-world evidence that immune checkpoint inhibitors offer longer treatment persistence but at higher costs compared to regorafenib or trifluridine/tipiracil in third-line advanced colorectal cancer. Addressing data gaps and economic challenges is essential to maximize the clinical and value-based benefits of immunotherapy in this setting.

References

1. NIH All of Us Research Program -- Duration of Treatment and Economic Viability of Third-Line Options for Advanced Colorectal Cancer